Impact Of Multidrug Resistance Research Articles

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003–2007) to 39.7% (2018–2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum β-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Impact of MDRs on COVID-19 Patients Among Developing Countries

Abstract: The COVID-19 virus has killed more than 6.3 million people worldwide. The misuse of antibiotics increased during epidemics, leading to the spread of MDRs. Although antibiotic use is increasing in both developed and developing countries, the utility level and abuse are higher in developing countries. This could have negative consequences for the vaccine, especially considering that many developing countries reported the emergence of many resistant microbes even before the pandemic. Infectious diseases, social and cultural pressures, and telemedicine facilities can all contribute to the overuse of antibiotics. The emergence of multidrug resistance is a major concern, especially in developing countries where health services are already inadequate and diagnostic capacity and facilities for disease prevention and control are inadequate. This might be the major cause of the extensive spread of such diseases. Improper waste management and disposal in hospitals and communities make it easy for clean water to leak from the area, causing many diseases and causing many antibiotics. The potential for microplastics to be turned into anti-bacterial products is also of particular concern for low- and middle-income countries. In the present review, we aim to examine the impact of multidrug resistance in ESKAPE infections coupled with healthcare-associated infections and determine their risk of secondary infection in COVID-19 patients in low- and middle-income countries during the COVID-19 epidemic from a multidisciplinary perspective, identify the challenge for developing countries and seek solutions to solve this problem.

Impact of multidrug resistance on the management of bacterial infections in cirrhosis.

Patients with cirrhosis have an increased risk of infection and differently from other complications, that over the years are improving in their outcomes, infections in cirrhotic patients are still a major cause of hospitalization and death (up to 50% in-hospital mortality). Infections by multidrug-resistant organisms (MDRO) have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact. About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years. MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution. An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects, such as the type of infection (spontaneous bacterial peritonitis, pneumonia, urinary tract infection and spontaneous bacteremia), bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition (community acquired, healthcare associated or nosocomial). Furthermore, regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology. Antibiotic treatment is the most effective measure to treat infections caused by MDRO. Therefore, optimizing antibiotic prescribing is critical to effectively treat these infections. Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality. On the other hand, the supply of new agents to treat these infections is very limited. Thus, specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.

Impact of multi-drug resistance on clinical outcomes of dogs with corneal ulcers infected with Staphylococcus pseudintermedius.

Compare characteristics and clinical outcomes of dogs with infectious keratitis from Staphylococcus pseudintermedius considered to be multidrug-resistant (MDR) or not. Staphylococcus pseudintermedius isolated as the primary pathogen from canine patients with ulcerative keratitis were considered MDR if resistant to at least one agent in three or more classes of antibiotics. Medical records were reviewed for history, patients' characteristics, clinical appearance, therapeutic interventions, and clinical outcomes. Twenty-eight dogs (28 eyes) were included. Compared to non-MDR cases, MDR diagnosis was significantly more common in dogs with recent (≤30 days) anesthesia (7/15 vs. 1/13, P = 0.038) and more common in non-brachycephalic dogs (8/15 vs. 2/13, P = 0.055). Clinical appearance (ulcer size/depth, anterior chamber reaction, etc.) did not differ significantly between groups (P ≥ 0.055). Median (range) time to re-epithelialization was longer in MDR vs. non-MDR eyes [29 (10-47) vs. 22 (7-42) days] but the difference was not significant (P = 0.301). Follow-up time was significantly longer in dogs with MDR keratitis [47 (29-590) vs. 29 (13-148) days, P = 0.009]. No other significant differences were noted between MDR and non-MDR eyes in regard to time for ulcer stabilization [4 (1-17) days vs. 4 (1-12), P = 0.699], number of eyes requiring surgical stabilization (7/15 vs. 7/13, P = 0.246) or enucleation (1/15 vs. 2/13, P = 1.000), success in maintaining globe (14/15 vs. 11/13, P = 0.583) or success in maintaining vision (12/15 vs. 10/13, P = 1.000). MDR infections may prolong corneal healing time but did not appear to affect overall clinical outcomes in dogs with bacterial keratitis. Further research is warranted in a larger canine population and other bacterial species.

Surgical Site Infection Following Caesarean Section by Acinetobacter Species: A Report from a Hyperendemic Setting in the Brazilian Amazon Region.

Surgical site infection (SSI) following caesarean section is associated with increased morbidity, mortality, and significant health care costs. This study evaluated the epidemiological, clinical, and microbiological features of Acinetobacter spp. in women with SSIs who have undergone caesarean section at a referral hospital in the Brazilian Amazon region. This study included 69 women with post-caesarean SSI by Acinetobacter spp. admitted to the hospital between January 2012 and May 2015. The 69 Acinetobacter isolates were subjected to molecular species identification, antimicrobial susceptibility testing, detection of carbapenemase-encoding genes, and genotyping. The main complications of post-caesarean SSI by Acinetobacter were inadequate and prolonged antibiotic therapy, sepsis, prolonged hospitalization, and re-suture procedures. A. baumannii, A. nosocomialis and A. colistiniresistens species were identified among the isolates. Carbapenem resistance was associated with OXA-23-producing A. baumannii isolates and IMP-1-producing A. nosocomialis isolate. Patients with multidrug-resistant A. baumannii infection showed worse clinical courses. Dissemination of persistent epidemic clones was observed, and the main clonal complexes (CC) for A. baumannii were CC231 and CC236 (Oxford scheme) and CC1 and CC15 (Pasteur scheme). This is the first report of a long-term Acinetobacter spp. outbreak in women who underwent caesarean section at a Brazilian hospital. This study demonstrates the impact of multidrug resistance on the clinical course of post-caesarean infections.

Bloodstream infections in older population: epidemiology, outcome, and impact of multidrug resistance

Bloodstream infections (BSIs) among older patients are frequent with high rate of mortality. Infections with multidrug-resistant organisms (MDRO) are associated with higher mortality than with susceptible microorganisms. We aimed to evaluate the prevalence of MDRO infection during BSI in older population and the factors associated with unfavorable outcome. This study is a retrospective cohort of all BSI episodes occurring among older patients (> 65yo), from April 1, 2010, to December 31, 2016, in a French university hospital for geriatric medicine. A total of 255 BSI episodes were analyzed. Mean age was 86.3±6.5 years, and sex ratio (M/F) was 0.96. Main comorbidities were orthopedic device (26.7%), active neoplasia (24.3%), and diabetes mellitus (18.4%). Main primary sites of infection were urinary tract infections (56.9%), respiratory tract infections (10.6%), intra-abdominal infections (7.1%), and skin and soft tissue infections (4.7%). Main bacteria identified were Escherichia coli (45.1%), Staphylococcus aureus (14.1%), enterococci (10.7%), coagulase-negative staphylococci (CoNS) (5.5%), and streptococci (5.1%). MDROs were involved in 17.2% of BSI (gram-negative bacilli: 9.0%; CoNS: 4.3%; and methicillin-resistant S. aureus (MRSA): 3.9%). The main factor associated with MDRO BSI was colonization with MDRO (OR=6.29; 95%CI=2.9-14.32). Total mortality was 18.4% and significantly higher in case of initial severity (OR=3.83; 95%CI=1.75-8.38), healthcare-associated infection (OR=5.29; 95%CI=1.11-25.30), and MRSA BSI (OR=9.16; 95%CI=1.67-50.16). BSI due to MDRO is frequent in older population and is strongly associated with carriage of MDRO. Healthcare-associated BSI, severe episodes, and BSI due to MRSA are associated with unfavorable outcome. In these cases, a broad-spectrum antibiotic should be promptly initiated.

Carriage of ESBL-producing Gram-negative bacteria by flies captured in a hospital and its suburban surroundings in Ethiopia

BackgroundLocal data from the Asella Teaching and Referral Hospital in the town of Asella, Ethiopia reveal a high prevalence of extended-spectrum β-lactamase- (ESBL) producing Gram-negative bacteria (GNB) in clinical isolates. To investigate a possible route of transmission, we determined the proportions ESBL-producing GNB in isolates from flies caught in the hospital and in the town of Asella.MethodsFlies were collected in August 2019 from the neonatal intensive care unit (NICU), the orthopedic ward, the hospital’s waste disposal area, and from a butchery situated 1.5 km from the hospital. After trapping, the flies were macerated and suspended in sterile normal saline. The suspensions were inoculated on MacConkey agar and incubated overnight. Species identification and antimicrobial susceptibility testing were performed using Vitek®-MS and VITEK® 2.ResultsIn total, 103 bacterial isolates were obtained from 85 flies (NICU: 11 isolates from 20 flies, orthopedic ward: 10 isolates from 12 flies, waste disposal area: 37 isolates from 26 flies, butchery: 45 isolates from 27 flies). The proportions of ESBL-producing bacteria among isolates obtained from flies collected in the hospital compound were significantly higher (82%, 90%, and 57% in NICU, orthopedic ward and waste disposal area, respectively) compared to flies collected outside of the hospital compound (2% (@1/45) in the butchery) (p ≤ 0.001). The proportion of ESBL was 67% (6/9) among Raoultella spp. 67% (4/6) among Kluyvera spp., 56% (5/9) among Enterobacter spp., 50% (5/10) among E. coli, and 44% (8/18) among Klebsiella spp.. Of the 40 ESBL-genes detected, 85% were CTX-M-like, 83% TEM-like, 23% SHV-like, and 2% CTX-M-2-like. ESBL-producing bacteria showed higher rates of resistance against ciprofloxacin (66% vs. 5%), gentamicin (68% vs. 3%), piperacillin-tazobactam (78% vs. 5%), and trimethoprim-sulfamethoxazole (88% vs. 16%), compared to non-ESBL-producing bacteria.ConclusionA high proportion of ESBL was identified in isolates from flies caught in the hospital compound compared with isolates of flies collected at a distance of 1.5 km from the hospital. Flies can be potential vectors for transmission of multidrug-resistant (MDR) bacteria within hospitals. Further studies are needed to determine the source of MDR colonization in flies and possible impact of MDR for nosocomial infections.

Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children

BackgroundThis study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa.MethodsA retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database.ResultsThe incidence risk of PABSI was 5.4 (95% CI: 4.34–6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality.ConclusionsPABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.

Epidemiology and Risk Factors Associated With Mortality in Consecutive Patients With Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria.

Background Mortality related to bloodstream infections (BSIs) is high. The epidemiology of BSIs is changing due to the increase in multidrug resistance, and it is unclear whether the presence of multidrug-resistant (MDR) organisms, per se, is an independent risk factor for mortality. Our objectives were, first, to describe the epidemiology and outcome of BSIs and, second, to determine the risk factors associated with mortality among patients with BSI.Methods This research used a single-center retrospective observational study design. Patients were identified through microbiological reports. Data on medical history, clinical condition, bacteria, antimicrobial therapy, and mortality were collected. The primary outcome was crude mortality at 30 days. The relationships between mortality and demographic, clinical, and microbiological variables were analyzed by multivariate analysis.Results A total of 1049 inpatients were included. MDR bacteria were isolated in 27.83% of patients, where 2.14% corresponded to an extremely drug-resistant (XDR) isolate. The crude mortality rates at days 7, 30, and 90 were 12.11%, 25.17%, and 36.13%, respectively. Pitt score >2, lung and abdomen as site of infection, and XDR Pseudomonas aeruginosa were independent risk factors for 7-, 30-, and 90-day mortality. Charlson score >4, carbapenem-resistant Klebsiella pneumoniae, and XDR Acinetobacter baumannii were independent risk factors for 30- and 90-day mortality. Infection by XDR gram-negative bacteria, Charlson score >4, and immunosuppression were independent risk factors for mortality in patients who were stable at the time of BSI.Conclusions BSI is an event with an extreme impact on mortality. Patients with severe clinical condition are at higher risk of death. The presence of XDR gram-negative bacteria in blood is strongly and independently associated with patient death.

CL2 SYSTEMATIC REVIEW AND METANALYSIS ON THE IMPACT OF MULTI-DRUG RESISTANT BACTERIA ON ECONOMIC AND CLINICAL OUTCOMES OF HEALTHCARE ACQUIRED INFECTIONS

Multidrug resistant (MDR) bacterial infections in hospital settings have substantial implications in terms of clinical and economic outcomes. However, due to the heterogeneity in resistance patterns, findings about the relationships between MDR infections and economic or clinical outcomes are currently under debate. We performed a systematic review and meta-analysis on the impact of MDR on clinical and economic outcomes, considering differences in the specific application, study design, and methodology. A literature search was conducted in PubMed/MEDLINE library database to select studies that evaluated the impact of antimicrobial resistance on economic and clinical outcomes, published in between 1980 and 2018. Next, a meta-analysis was performed to establish the adjusted association of MDR hospital acquired infection (HAI) with direct cost of care, prolonged length of stay and mortality. Overall, 23 articles were included in the systematic review of which 12 articles assessed cost, 13 articles assessed length of stay, and 12 assessed mortality. The pooled mean ratios with 95% confidence intervals (95%CI) were 1.55 (95%CI=1.49; 1.62) for direct cost of care was and 1.23 (95%CI=1.20; 1.27) for length of stay, respectively. The hazard rate for mortality was 2.27 (95%CI=2.13; 2.41). Statistical and methodological heterogeneity among the included studies was found to be present. MDR HAI appears to be strongly associated with increases in direct cost, prolonged length of stay and increased mortality. Further comprehensive studies in this setting are warranted.

Bacteraemia due to extensively drug-resistant Pseudomonas aeruginosa sequence type 235 high-risk clone: Facing the perfect storm

Predictors of mortality and the impact of multidrug resistance and virulence on patients with Pseudomonas aeruginosa (PA) bacteraemia were evaluated. Patients with PA bacteraemia in a 12-month period were retrospectively analysed. Carbapenemase production, molecular typing and identification of virulence factor ExoU were carried out. The activity of ceftolozane-tazobactam and ceftazidime-avibactam was also investigated. The primary endpoint was 30-day crude mortality. Of 64 patients with bacteraemia, 24 (37.5%) were caused by extensively drug-resistant PA (XDR-PA): 10 (41.7%) cases involved the VIM-2 carbapenemase-producing ST175 clone, 11 (45.8%) the GES-5 carbapenemase-producing ST235 clone, and 3 (12.5%) were non-carbapenemase producers. The exoU genotype was detected in all ST235 strains and in 6 (15%) of the non-XDR isolates. Ceftazidime-avibactam (58.3%) showed greater activity than ceftolozane-tazobactam (12.5%) against XDR-PA isolates, particularly in GES-5 producers (100%). The 30-day crude mortality rate in patients with XDR-PA bacteraemia was higher than in cases caused by susceptible strains (62.5% vs. 30%; P=0.02). Multivariate analysis showed that independent risk factors associated with 30-day crude mortality were Pitt score ≥2 (OR, 42.31; 95% CI, 4.88-366.7; P=0.001) and respiratory source of bacteraemia (OR, 49.13; 95% CI 3.89-620.5; P=0.003). Stratified analysis adjusting for respiratory source revealed a non-significant trend towards higher mortality in patients with bacteraemia caused by the ST235 clone and exoU-producing isolates. These data support the notion that the XDR phenotype associated with the GES-5 carbapenemase-producing ST235 clone and the exoU-positive genotype adversely affects the outcome of patients with PA bacteraemia, particularly those with respiratory tract infections and a severe clinical presentation.

Bacterial Infections After Burn Injuries: Impact of Multidrug Resistance.

Patients who are admitted to the hospital after sustaining a large burn injury are at high risk for developing hospital-associated infections. If patients survive the initial 72 hours after a burn injury, infections are the most common cause of death. Ventilator-associated pneumonia is the most important infection in this patient population. The risk of infections caused by multidrug-resistant bacterial pathogens increases with hospital length of stay in burn patients. In the first days of the postburn hospitalization, more susceptible, Gram-positive organisms predominate, whereas later more resistant Gram-negative organisms are found. These findings impact the choice of empiric antibiotics in critically ill burn patients. A proactive infection control approach is essential in burn units. Furthermore, a multidisciplinary approach to burn patients with a team that includes an infectious disease specialist and a pharmacist in addition to the burn surgeon is highly recommended.

Impact Of Multi-Drug Resistance On HTA Assessment Of Antibiotics In France, Germany, United Kingdom

Impact Of Multi-Drug Resistance On HTA Assessment Of Antibiotics In France, Germany, United Kingdom

Prevalence of multi drug antimicrobial resistance in Mannheimia haemolytica isolated from high-risk stocker cattle at arrival and two weeks after processing1

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in North American beef cattle. () is the bacterial pathogen most frequently isolated from cattle with BRD and the prevalence of antimicrobial resistance in this pathogen has been increasing. Administration of antimicrobials to prevent BRD is commonplace in stocker cattle, but the impact of this practice on emergence of resistance in is unknown. High risk, sale barn origin bull and steer calves ( = 169) were transported to a stocker facility in central Georgia and sampled via deep nasopharyngeal swab (NPS) at arrival processing. All calves received the macrolide antimicrobial tulathromycin (2.5 mg/kg subcutaneously) at arrival processing. A second NPS was collected from each calf 10 to 14 d after arrival. The occasional calves diagnosed and treated for BRD prior to 10 to 14 d were swabbed and cultured prior to treatment. Swabs were submitted for culture and antimicrobial susceptibility testing using the Kirby-Bauer disk diffusion method. Of the 169 cattle enrolled, 27 (16.0%) were culture positive for at arrival processing and of these, a multi-drug resistant (MDR) strain of was detected in 1 (3.7%). In contrast, 123 (72.8%) cattle were culture positive for at second sampling and of these, a MDR strain of was detected in 122 (99.2%). The proportions of cattle culture positive for and positive for MDR at arrival processing and at second sampling were significantly different ( < 0.001). At the level of the individual bacterial isolate, 366 individual isolates were collected from the calves at the time of the second sampling. Of these isolates, 361 (98.6%) were intermediate or resistant to all macrolides tested (tilmicosin, gamithromycin, tulathromycin) and the fluoroquinolone enrofloxacin. In addition, 254 isolates (69.4%) were intermediate or resistant to florfenicol and 4 (1.1%) were intermediate or resistant to ceftiofur. There was a significant difference in the proportion of isolates resistant to all of the drug classes except cephalosporins at arrival processing versus second sampling ( < 0.001). Our results show that there was an increase in the proportion of calves positive for from arrival processing to second sampling, and that there was an increase in the proportion of calves that had MDR strains of detected from arrival processing to second sampling. More research is needed to understand the role of metaphylaxis on MDR in and the impact of MDR on morbidity and mortality in stocker cattle.

Bacterial Infections after Burn Injuries: Impact of Multidrug Resistance

Bacterial Infections after Burn Injuries: Impact of Multidrug Resistance

Impact of Multidrug-resistant Enterobacteriaceae Bloodstream Infections in Children

BackgroundAntibiotic resistance is a serious and growing concern worldwide. Although Enterobacteriaceae bloodstream infections (BSI) are severe, little is known regarding the impact of multidrug resistance (MDR) on children. This study aimed to describe the clinical and microbiological features of MDR Enterobacteriaceae BSI in a children’s hospital in Japan.MethodsChildren (<18 years of age) presenting with Enterobacteriaceae BSI at Tokyo Metropolitan Children’s Medical Center in Japan between March 2010 and March 2017 were enrolled. The clinical characteristics and outcomes of patients with MDR and non-MDR Enterobacteriaceae BSI were compared. The Centers for Disease Control and Prevention’s definition of MDR was used for this study.ResultsIn total 134 blood cultures from 127 patients were analyzed. The median age was 3.6 years (IQR: 0.3–9.8 years), and boys accounted for 52.8% of the subject pool. Underlying diseases were noted in 92.1% of patients. In 79.1%, BSI developed >48 hours after admission. The most common isolate was Escherichia coli (47.0%) followed by Klebsiella pneumoniae (23.1%). MDR was detected in 35.8% (48/134) of culture, with Escherichia coli occurring with the highest frequency (23.1%) followed by Klebsiella pneumoniae (7.5%). The MDR strains producing ESBL, AmpC, and carbapenemases comprised 17.9%, 7.5%, and 1.5% of the cases, respectively. Multivariate logistic regression analysis showed that the history of corticosteroid use within 30 days was independently associated with the development of MDR Enterobacteriaceae BSI (OR: 3.63; 95% CI: 1.35–9.73). Initial empiric therapy was less effective against MDR, than non-MDR, strains (51.1% vs. 83.8%, P < 0.001). MDR was not significantly associated with an increased rate of all-cause mortality (MDR 10.4% vs. non-MDR 3.5%, P = 0.134) or sepsis-related mortality (MDR 6.3% vs. non-MDR 2.3%, P = 0.349).ConclusionA history of corticosteroid use within 30 days was an independent risk factor for the development of MDR Enterobacteriaceae BSI in children. MDR did not increase the mortality rate significantly.Disclosures All authors: No reported disclosures.

Healthcare-Associated Infections in Pediatric and Neonatal Intensive Care Units: Impact of Underlying Risk Factors and Antimicrobial Resistance on 30-Day Case-Fatality in Italy and Brazil.

OBJECTIVES To describe trends in the epidemiology of healthcare-associated Infections (HAIs) in pediatric/neonatal intensive care units (ICUs) and to evaluate risk factors and impact of multidrug resistance in children admitted to ICUs. DESIGN Multicenter, retrospective, cohort study with a nested case-control study conducted from January 1, 2010, through December 31, 2014. SETTING Three tertiary care pediatric hospitals in Italy and Brazil with a total of 103 ICU beds. PATIENTS Inclusion criteria were admission to ICU during the study period, age at onset less than 18 years, and microbiologically confirmed HAI. RESULTS A total of 538 HAIs in 454 children were included; 93.3% of patients had comorbidities. Bloodstream infections were the leading pattern (45.4%). The cumulative incidence of HAI was 3.6/100 ICU admissions and the crude 30-day fatality rate was 5.7/1,000 admissions. The most frequently isolated pathogens were Enterobacteriaceae, followed by Pseudomonas aeruginosa and Staphylococcus aureus. Forty-four percent of isolates were multidrug-resistant (MDR). Two multivariate logistic regressions were performed. Factors independently associated with an MDR-HAI were country, previous antibiotics, transplantation, major surgery, and colonization by an MDR strain. Factors independently associated with 30-day case fatality were country, previous transplantation, fungal infection, bloodstream infection, lower respiratory tract infection, and infection caused by MDR strains. CONCLUSIONS Infection control and prevention can limit the spread of MDR strains and improve outcomes. Targeted surveillance programs collecting neonatal and pediatric HAI/bloodstream infection data and outcomes would allow global benchmarking. The next step is to identify methods to monitor key HAIs and integrate these into affordable intervention programs. Infect Control Hosp Epidemiol 2016;1-8.

Bloodstream infections caused by multi-drug resistant Proteus mirabilis: Epidemiology, risk factors and impact of multi-drug resistance

ABSTRACTBackground The prevalence of antimicrobial co-resistance among ESBL-producing Enterobactereaceae is extremely high in Israel. Multidrug-resistant Proteus mirabilis strains (MDR-PM), resistant to almost all antibiotic classes have been described. The aim was to determine the risk factors for bloodstream infections caused by MDR-PM and clinical outcomes. Methods A retrospective case-control study. Adult patients with PM bacteremia during 7 years were identified retrospectively and their files reviewed for demographics, underlying diseases, Charlson Comorbidity Index, treatment and outcome. Results One hundred and eighty patients with PM-bloodstream infection (BSI) were included; 90 cases with MDR-PM and 90 controls with sensitive PM (S-PM). Compared to controls, cases more frequently were from nursing homes, had recurrent hospital admissions in the past year and received antibiotic therapy in the previous 3 months, were bedridden and suffered from peripheral vascular disease and peptic ulcer disease (p < 0.001). Two-thirds of the MDR-PM isolates were ESBL-producers vs 4.4% of S-PM isolates (p < 0.001, OR = 47.6, 95% CI = 15.9–142.6). In-hospital crude mortality rate of patients with MDR-PM BSI was 37.7% vs 23.3% in those with S-PM BSI (p = 0.0359, OR = 2, 95% CI = 1.4–3.81). Conclusions PM bacteremia in elderly and functionally-dependent patients is likely to be caused by nearly pan-resistant PM strains in the institution; 51.8% of the patients received inappropriate empiric antibiotic treatment. The crude mortality rate of patients with MDR-PM BSI was significantly higher than that of patients with S-PM BSI.

Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study.

IntroductionThe impact of in vitro resistance on initially appropriate antibiotic therapy (IAAT) remains unclear. We elucidated the relationship between non-IAAT and mortality, and between IAAT and multi-drug resistance (MDR) in sepsis due to Gram-negative bacteremia (GNS).MethodsWe conducted a single-center retrospective cohort study of adult intensive care unit patients with bacteremia and severe sepsis/septic shock caused by a gram-negative (GN) organism. We identified the following MDR pathogens: MDR P. aeruginosa, extended spectrum beta-lactamase and carbapenemase-producing organisms. IAAT was defined as exposure within 24 hours of infection onset to antibiotics active against identified pathogens based on in vitro susceptibility testing. We derived logistic regression models to examine a) predictors of hospital mortality and b) impact of MDR on non-IAAT. Proportions are presented for categorical variables, and median values with interquartile ranges (IQR) for continuous.ResultsOut of 1,064 patients with GNS, 351 (29.2%) did not survive hospitalization. Non-survivors were older (66.5 (55, 73.5) versus 63 (53, 72) years, P = 0.036), sicker (Acute Physiology and Chronic Health Evaluation II (19 (15, 25) versus 16 (12, 19), P <0.001), and more likely to be on pressors (odds ratio (OR) 2.79, 95% confidence interval (CI) 2.12 to 3.68), mechanically ventilated (OR 3.06, 95% CI 2.29 to 4.10) have MDR (10.0% versus 4.0%, P <0.001) and receive non-IAAT (43.4% versus 14.6%, P <0.001). In a logistic regression model, non-IAAT was an independent predictor of hospital mortality (adjusted OR 3.87, 95% CI 2.77 to 5.41). In a separate model, MDR was strongly associated with the receipt of non-IAAT (adjusted OR 13.05, 95% CI 7.00 to 24.31).ConclusionsMDR, an important determinant of non-IAAT, is associated with a three-fold increase in the risk of hospital mortality. Given the paucity of therapies to cover GN MDRs, prevention and development of new agents are critical.

The impact of multidrug resistance on outcomes in ventilator-associated pneumonia

Multidrug-resistant (MDR) organisms in ventilator-associated pneumonia were found in 49 of 107 patients and were associated with home antibiotics, pre-ventilator-associated pneumonia hospital stay, and health care exposure. Overall, MDR organisms were associated with increased mortality (P = .006). On multivariate analysis, MDR status was modulated by organism class. In nonfermenting gram-negative rods, no association between MDR and mortality was found, but, in all other organisms, MDR was associated with increased mortality risk (hazard ratio, 6.15; 95% confidence interval: 1.80-21.05, P = .004).